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Acanthocephalans are parasites with complex lifecycles that are important components of aquatic systems and are often model species for parasite-mediated host manipulation. Genetic characterization has recently resurrected Pomphorhynchus tereticollis as a distinct species from Pomphorhynchus laevis, with potential implications for fisheries management and host manipulation research. Morphological and molecular examinations of parasites from 7 English rivers across 9 fish species revealed that P. tereticollis was the only Pomphorhynchus parasite present in Britain, rather than P. laevis as previously recorded. Molecular analyses included two non-overlapping regions of the mitochondrial gene - cytochrome oxidase and generated 62 sequences for the shorter fragment (295 bp) and 74 for the larger fragment (583 bp). These were combined with 61 and 13 sequences respectively, from Genbank. A phylogenetic analysis using the two genetic regions and all the DNA sequences available for P. tereticollis identified two distinct genetic lineages in Britain. One lineage, possibly associated with cold water tolerant fish, potentially spread to the northern parts of Britain from the Baltic region via a northern route across the estuarine area of what is now the North Sea during the last Glaciation. The other lineage, associated with temperate freshwater fish, may have arrived later via the Rhine/Thames fluvial connection during the last glaciation or early Holocene when sea levels were low. These results raise important questions on this generalist parasite and its variously environmentally adapted hosts, and especially in relation to the consequences for parasite vicariance.

A general framework is presented that should enhance our understanding of how intrinsic factors, such as body size, and extrinsic factors, such as climate, affect the dynamics and demographics of fish populations. Effects of intrinsic factors, notably studies relating juvenile Atlantic salmon Salmo salar body size to their probability to return as an adult, are often context-dependent and anecdotal, due to data constraints. By merit of its flexible specification, this framework should admit datasets with a range of situation-specific nuances, collected using different approaches, and thereby deliver more general and robust findings for more effective population management., (© 2018 The Fisheries Society of the British Isles.)

Populations of fishes provide valuable services for billions of people, but face diverse and interacting threats that jeopardize their sustainability. Human population growth and intensifying resource use for food, water, energy and goods are compromising fish populations through a variety of mechanisms, including overfishing, habitat degradation and declines in water quality. The important challenges raised by these issues have been recognized and have led to considerable advances over past decades in managing and mitigating threats to fishes worldwide. In this review, we identify the major threats faced by fish populations alongside recent advances that are helping to address these issues. There are very significant efforts worldwide directed towards ensuring a sustainable future for the world's fishes and fisheries and those who rely on them. Although considerable challenges remain, by drawing attention to successful mitigation of threats to fish and fisheries we hope to provide the encouragement and direction that will allow these challenges to be overcome in the future., (© 2018 The Authors. Journal of Fish Biology published by John Wiley & Sons Ltd on behalf of The Fisheries Society of the British Isles.)

Populations of generalist species often comprise of smaller sub-sets of relatively specialized individuals whose niches comprise small sub-sets of the overall population niche. Here, the role of parasite infections in trophic niche specialization was tested using five wild fish populations infected with the non-native parasite Ergasilus briani, a copepod parasite with a direct lifecycle that infects the gill tissues of fish hosts. Infected and uninfected fishes were sampled from the same habitats during sampling events. Prevalence in the host populations ranged between 16 and 67%, with parasite abundances of up to 66 parasites per fish. Although pathological impacts included hyperplasia and localized haemorrhaging of gill tissues, there were no significant differences in the length, weight and condition of infected and uninfected fishes. Stable isotope analyses (δ 13C, δ 15N) revealed that the trophic niche of infected fishes, measured as standard ellipse area (i.e. the isotopic niche), was consistently and significantly smaller compared with uninfected conspecifics. These niches of infected fishes always sat within that of uninfected fish, suggesting trophic specialization in hosts. These results suggested trophic specialization is a potentially important non-lethal consequence of parasite infection that results from impaired functional traits of the host.

Environmental DNA (eDNA) detection of non-native species has considerable potential to inform management decisions, including identifying the need for population control and/or eradication. An invasive species of European concern is the Asian cyprinid fish, topmouth gudgeon (Pseudorasbora parva). Here, eDNA analyses were applied at a commercial angling venue in southern England to inform operations aiming to eradicate P. parva, which had only ever been observed in one of the venue's seven unconnected angling ponds. Eradication of P. parva was initially attempted by repeated depletion of the population using fish traps (crayfish traps fitted with 5 mm mesh netting) and the introduction of native predators over a 4-year period. The very low number of P. parva captured following these eradication efforts suggested a possible population crash. Conventional PCR analysis of water samples using species-specific primers was applied to all seven ponds to confirm that P. parva was present in only one pond, that the eradication attempt had indeed failed and that the species' distribution in the pond appeared to be restricted to three bankside locations. The continued presence of P. parva at these locations was confirmed by subsequent trapping. Water samples from an adjacent, unconnected stream were also analysed using the eDNA methodology, but no DNA of P. parva was detected. The results suggest that further management action to eradicate P. parva be focused on the pond shown to contain the isolated P. parva population and thereby eliminate the risk of further dispersal. This study is the first to apply eDNA analysis to assess the efficacy of an eradication attempt and to provide evidence that the species was unlikely to be present in the other ponds, thus reducing the resources needed to control the species.

Objective: To assess the association between delivery room (DR) continuous positive airway pressure (CPAP) and pneumothorax (PT) in term newborns., Methods: Two studies performed in community hospitals used data extracted from computerized records of term newborns. Infants receiving positive pressure ventilation in the DR were excluded. Tabulated data included receipt of DR CPAP, PT on the day of birth, and gestational age (GA). In a case-control study from 2001-2013, infants with PT were compared to controls without PT but with respiratory distress or hypoxia persisting from birth for receipt of DR CPAP. In a cohort study from 2014-2016, infants receiving and not receiving DR CPAP were compared for the incidence of PT., Results: In the case-control study, data were obtained for 169 cases and 850 controls. Compared to controls, PT infants were more likely to have received DR CPAP (16.8% vs. 40.2%, respectively, P < 0.001). Logistic regression revealed DR CPAP (Adjusted Odds Ratio [AOR] = 3.30, 95% confidence interval [CI] = 2.31, 4.72, P < 0.001) and GA (AOR = 1.21, 95% CI = 1.05, 1.39, P = 0.009) to be independent predictors of early PT.In the cohort study, PT was observed in 0.1% of 9255 control infants not receiving DR CPAP and 4.8% of 228 infants receiving DR CPAP (P < 0.001). In logistic regression analyses, DR CPAP significantly predicted PT (OR = 59.59, 95% CI = 23.34, 147.12, P < 0.001) and remained a significant predictor of PT after controlling for gestational age., Conclusion: Respiratory conditions treated with CPAP in delivery rooms are associated with increased risk of PT. A cause-and-effect relationship between CPAP and PT cannot be claimed in this study. Further research is needed to better understand this relationship.

This paper presents the first phase in the development and validation of a simple and reliable environmental (e)DNA method using conventional PCR to detect four species of non-native freshwater fish: pumpkinseed Lepomis gibbosus, sunbleak Leucaspius delineatus, fathead minnow Pimephales promelas and topmouth gudgeon Pseudorasbora parva. The efficacy of the approach was demonstrated in indoor tank (44 l) trials in which all four species were detected within 24 h. Validation was through two field trials, in which L. gibbosus was detected 6-12 h after its introduction into outdoor experimental ponds and P. parva was successfully detected in disused fish rearing ponds where the species was known to exist. Thus, the filtration of small (30 ml) volumes of pond water was sufficient to capture fish eDNA and the approach emphasised the importance of taking multiple water samples of sufficient spatial coverage for detecting species of random or patchy distribution., (© 2016 Crown copyright. Journal of Fish Biology © 2016 The Fisheries Society of the British Isles.)

Predicting fish responses to modified flow regimes is becoming central to fisheries management. In this study we present an agent-based model (ABM) to predict the growth and distribution of young-of-the-year (YOY) and one-year-old (1+) Atlantic salmon and brown trout in response to flow change during summer. A field study of a real population during both natural and low flow conditions provided the simulation environment and validation patterns. Virtual fish were realistic both in terms of bioenergetics and feeding. We tested alternative movement rules to replicate observed patterns of body mass, growth rates, stretch distribution and patch occupancy patterns. Notably, there was no calibration of the model. Virtual fish prioritising consumption rates before predator avoidance replicated observed growth and distribution patterns better than a purely maximising consumption rule. Stream conditions of low predation and harsh winters provide ecological justification for the selection of this behaviour during summer months. Overall, the model was able to predict distribution and growth patterns well across both natural and low flow regimes. The model can be used to support management of salmonids by predicting population responses to predicted flow impacts and associated habitat change.

Predicting regions at risk from introductions of non-native species and the subsequent invasions is a fundamental aspect of horizon scanning activities that enable the development of more effective preventative actions and planning of management measures. The Asian cyprinid fish topmouth gudgeon Pseudorasbora parva has proved highly invasive across Europe since its introduction in the 1960s. In addition to direct negative impacts on native fish populations, P. parva has potential for further damage through transmission of an emergent infectious disease, known to cause mortality in other species. To quantify its invasion risk, in regions where it has yet to be introduced, we trained 900 ecological niche models and constructed an Ensemble Model predicting suitability, then integrated a proxy for introduction likelihood. This revealed high potential for P. parva to invade regions well beyond its current invasive range. These included areas in all modelled continents, with several hotspots of climatic suitability and risk of introduction. We believe that these methods are easily adapted for a variety of other invasive species and that such risk maps could be used by policy-makers and managers in hotspots to formulate increased surveillance and early-warning systems that aim to prevent introductions and subsequent invasions.

In host-parasite relationships, parasite prevalence and abundance can vary over time, potentially impacting how hosts are affected by infection. Here, the pathology, growth, condition and diet of a juvenile Cyprinus carpio cohort infected with the non-native cestode Bothriocephalus acheilognathi was measured in October 2012 (end of their first summer of life), April 2013 (end of first winter) and October 2013 (end of second summer). Pathology revealed consistent impacts, including severe compression and architectural modification of the intestine. At the end of the first summer, there was no difference in lengths and condition of the infected and uninfected fish. However, at the end of the winter period, the condition of infected fish was significantly reduced and by the end of their second summer, the infected fish were significantly smaller and remained in significantly reduced condition. Their diets were significantly different over time; infected fish consumed significantly higher proportions of food items <53 µm than uninfected individuals, a likely consequence of impaired functional traits due to infection. Thus, the sub-lethal impacts of this parasite, namely changes in histopathology, growth and trophic niche were dependent on time and/or age of the fish.

The changes in the fish assemblage of the Capivara Reservoir, Brazil, were assessed over a 20 year period. Of 50 native fishes present in the initial samples, 27 were no longer present in the final samples, but there had been an addition of 11 invasive fishes, suggesting the occurrence of substantial shifts in fish diversity and abundance., (© 2014 The Fisheries Society of the British Isles.)

The effects of number of fish that are aged and scale sub-sampling strategies on the precision of estimates of mean age-length increments from populations of Rutilus rutilus, Leuciscus leuciscus and Leuciscus cephalus were tested. Analyses used data derived from river fish communities in eastern England, U.K.. Regarding the number of fishes analysed in each age group, for each species and mean fork-length increment at age, significant relationships were detected between sample size (n) and the coefficient of variation of the mean (Z) and mean length increment x‾ and measured variance (s(2)). This enabled calculation of the number of scales for producing a mean length increment at age according to n=ax‾(b(-2))Zx‾(-2). Outputs indicated that the number of scales requiring ageing increased substantially as precision increased, but with little variation between species per age category. Ageing between seven and 12 scales per age group would thus provide estimates at 10% precision. As the ages of fishes are not known in advance of scale ageing, the effect of scale sub-sampling regime on precision was also tested using randomized strategies of 10 fish per 5 mm, five per 5 mm, three per 5 mm, 10 per 10 mm, five per 10 mm and three per 10 mm. These were applied to the datasets and the consequences of their reduction in the number of scales for precision were determined using Z=a(0.5)x‾((b/2)(-1))n(-0.5). When compared to no sub-sampling, three per 10 mm always significantly reduced data precision, whereas 10 per 5 mm never significantly reduced precision. These outputs can thus be applied to the design of fish sampling protocols where age and growth estimates are required, with the randomized sub-sampling likely to be the most useful strategy., (© 2014 The Fisheries Society of the British Isles.)

Despite growing concern of the ecological risks posed by the European catfish Siluris glanis L. in freshwater fisheries, little information exists on the parasite fauna of this silurid catfish in Britain. Parasitological examinations of released S. glanis from four still-water fisheries in England revealed the presence of Thaparocleidus vistulensis (Siwak, 1932) and Ergasilus sieboldi (Nordmann, 1832), both non-native parasites, the latter known to be an important fish pathogen. This represents the first record of T. vistulensis from British freshwater fish. The human-assisted movement of S. glanis between UK recreational still-water fisheries provides a clear avenue for the introduction and spread of non-native parasites.

Objective: The definition of bronchopulmonary dysplasia (BPD) among very-low birth weight (VLBW) infants is based upon oxygen requirement at 36 weeks gestation, but oxygen may be required at altitude because of hypoxia. This study determined the effect of altitude on BPD rates., Study Design: For 63 VLBW infants at high altitude, oxygen concentrations were measured by a hood oxygenation test (HOT) and BPD rates were determined with altitude adjustment., Result: BPD rates before and after altitude adjustment were 71.8 and 26.7%, respectively. Of oxygen-dependent infants analyzed by HOT, 33.3% needed room air. HOT oxygen requirement correlated with gestational age of last apnea episode (r=0.42, P<0.001)., Conclusion: Although BPD rates may be adjusted for altitude with the HOT, the test does not accurately predict clinical oxygen need. Persistent requirement for supplemental oxygen beyond that needed in the HOT may be partially due to immaturity of respiratory control mechanisms.

Hatchery-reared and wild roach Rutilus rutilus were correctly classified to their rearing environment in a discriminant function using data on their scale circuli patterns. The discriminant function was then used to classify recaptured R. rutilus by their origin (hatchery-reared and wild) during a riverine stocking evaluation. At 8 and 18 months post-stocking, 10 and 7% of fish captured in the vicinity of the stocking site were classified as hatchery-reared., (© 2010 The Author. Journal of Fish Biology © 2010 The Fisheries Society of the British Isles.)

Background: Epidemiological studies suggest that hookworm infection protects against asthma, and therefore that hookworm infection may have a direct or an indirect therapeutic potential in this disease. We now report the first clinical trial of experimental hookworm infection in people with allergic asthma., Objectives: To determine the effects of experimental hookworm infection in asthma., Methods: Thirty-two individuals with asthma and measurable airway responsiveness to adenosine monophosphate (AMP) were randomized and double blinded to cutaneous administration of either ten Necator americanus larvae, or histamine solution (placebo), and followed for 16 weeks. The primary outcome was the change in provocation dose of inhaled AMP required to reduce forced expiratory volume in 1 s by 20% (PD(20)AMP) from baseline to week 16. Secondary outcomes included change in several measures of asthma control and allergen skin sensitivity and the occurrence of adverse effects., Results: Mean PD(20)AMP improved in both groups, more in the hookworm [1.49 doubling doses (DD)] than the placebo group (0.98 DD), but the difference between groups was not significant (0.51 DD; 95% confidence interval: -1.79 to 2.80; P=0.65). There were no significant differences between the two groups for other measures of asthma control or allergen skin sensitization. Infection was generally well tolerated., Conclusions: Experimental infection with ten hookworm larvae in asthma did not result in significant improvement in bronchial responsiveness or other measures of asthma control in this study. However, infection was well tolerated and resulted in a non-significant improvement in airway responsiveness, indicating that further studies that mimic more closely natural infection are feasible and should be undertaken.

Within the distribution of Ligula intestinalis, a tapeworm affecting freshwater fishes, there are genetically distinct and well-separated phylogenetic clusters. East Africa is represented by a single monophyletic clade which is understudied compared with Euro-Mediterranean clades. The present field investigation in the Lake Baringo and Naivasha catchments, Kenya, revealed that this L. intestinalis clade was highly host-specific, present in only 2 of 12 fishes examined; Barbus paludinosus in Naivasha and Barbus lineomaculatus in Baringo. In infected fish, cestodes comprised up to 20% of body weight. Only 1 parasite was recorded per fish, a contrast to infected fishes in Europe where mixed infections are commonplace. In B. lineomaculatus in Baringo, only fish of greater than 64 mm in length were parasitized. The highest parasite prevalence was recorded in fish of 70-77 mm in length, and reduced for lengths of 78-84 mm. Parasitized fish were significantly associated with a particular type of habitat, occurring most frequently in shallow littoral areas, and being absent from open water and rocky shore habitats. Uninfected fish were present in all habitats. This relationship between spatial occupancy and parasite prevalence is suggested to arise from behavioural alterations induced by the parasite that promotes completion of the parasite life cycle.

Background: Epidemiological studies suggest that dietary intake of vitamins A, C and E may be associated with the occurrence of asthma. A systematic review and meta-analysis was conducted in accordance with MOOSE guidelines to determine whether vitamins A, C and E, measured as dietary intakes or serum levels, are associated with asthma., Methods: MEDLINE, EMBASE, CINAHL, CAB abstracts and AMED (up to November 2007), conference proceedings and bibliographies of papers were searched to identify studies of asthma, wheeze or airway responsiveness in relation to intakes and serum concentrations of vitamins A, C and E. Pooled odds ratios (OR) or mean differences (MD) with 95% confidence intervals (CI) were estimated using random effects models., Results: A total of 40 studies were included. Dietary vitamin A intake was significantly lower in people with asthma than in those without asthma (MD -82 microg/day, 95% CI -288 to -75; 3 studies) and in people with severe asthma than in those with mild asthma (MD -344 microg/day; 2 studies). Lower quantile dietary intakes (OR 1.12, 95% CI 1.04 to 1.21; 9 studies) and serum levels of vitamin C were also associated with an increased odds of asthma. Vitamin E intake was generally unrelated to asthma status but was significantly lower in severe asthma than in mild asthma (MD -1.20 microg/day, 95% CI -2.3 to -0.1; 2 studies)., Conclusions: Relatively low dietary intakes of vitamins A and C are associated with statistically significant increased odds of asthma and wheeze. Vitamin E intake does not appear to be related to asthma status.

A high fruit intake may reduce the risk of asthma. The English National School Fruit Scheme was introduced in the East Midlands region of the UK in June 2003 and in the Eastern region in September 2004. Questionnaires were distributed to children aged 4-6 yrs in schools in May 2003. This was repeated in May 2004 when those in the East Midlands had received free fruit for 1 yr and those in the Eastern region had not. Responses were obtained in 2004 for 4,971 (53%) and 5,770 (54%) children in the intervention and control regions, respectively. Despite an increase in fruit consumption in the intervention compared with the control region between 2003 and 2004, there was no difference between the two regions in the prevalence or severity of asthma symptoms after 1 yr of fruit supplementation (odds ratio for wheeze in the past 12 months in intervention compared with control region 1.00, 95% confidence interval 0.88-1.14). Providing free fruit at school for 1 yr does not have any immediate effect on prevalence or severity of asthma in young children, although these data do not refute the hypothesis that a higher increase in fruit intake improves measures of asthma control.

Objective: To test the hypothesis that obstructive sleep apnoea (OSA) is more common in pregnancies complicated by hypertensive disease and fetal growth restriction., Study Design: An observational study comparing pregnant women with these two complications with normal pregnant women and non-pregnant women in two UK maternity hospitals. Each participant completed a sleep apnoea questionnaire and underwent nocturnal oxygen saturation monitoring., Results: Using a strict definition of obstructive sleep apnoea confirmed by oxygen saturation monitoring only two mild cases were seen, 0/50 non-pregnant women, 1/69 of normal pregnant women, 0/48 women with various types of hypertensive disease, and 1/33 women carrying fetuses affected with fetal growth restriction. Even using less strict definitions and self-reported sleepiness scores there was no relation between sleep apnoea and either fetal growth restriction or hypertensive diseases., Conclusion: Obstructive sleep apnoea is at most a rare cause of either growth restriction or hypertensive disease in pregnancy.

Background: Varenicline, a new treatment for smoking cessation, has demonstrated significantly greater efficacy over placebo and sustained release bupropion (bupropion SR). A study was undertaken to compare a 12-week standard regimen of varenicline with a 10-week standard regimen of transdermal nicotine replacement therapy (NRT) for smoking cessation., Methods: In this 52-week, open-label, randomised, multicentre, phase 3 trial conducted in Belgium, France, The Netherlands, UK and USA, participants were randomly assigned (1:1) to receive varenicline uptitrated to 1 mg twice daily for 12 weeks or transdermal NRT (21 mg/day reducing to 7 mg/day) for 10 weeks. Non-treatment follow-up continued to week 52. The primary outcome was the biochemically confirmed (exhaled carbon monoxide < or = 10 ppm) self-reported continuous abstinence rate (CAR) for the last 4 weeks of the treatment period in participants who had taken at least one dose of treatment. Secondary outcomes included CAR from the last 4 weeks of treatment through weeks 24 and 52, and measures of craving, withdrawal and smoking satisfaction., Results: A total of 376 and 370 participants assigned to varenicline and NRT, respectively, were eligible for analysis. The CAR for the last 4 weeks of treatment was significantly greater for varenicline (55.9%) than NRT (43.2%; OR 1.70, 95% CI 1.26 to 2.28, p<0.001). The week 52 CAR (NRT, weeks 8-52; varenicline, weeks 9-52) was 26.1% for varenicline and 20.3% for NRT (OR 1.40, 95% CI 0.99 to 1.99, p = 0.056). Varenicline significantly reduced craving (p<0.001), withdrawal symptoms (p<0.001) and smoking satisfaction (p<0.001) compared with NRT. The most frequent adverse event was nausea (varenicline, 37.2%; NRT, 9.7%)., Conclusions: The outcomes of this trial established that abstinence from smoking was greater and craving, withdrawal symptoms and smoking satisfaction were less at the end of treatment with varenicline than with transdermal NRT., Trial Registration Number: NCT00143325.

Respiratory failure is an important terminal event in muscular dystrophy, but increasingly is effectively treated by non-invasive ventilation. This study was designed to assess mortality statistics in this patient group in order to get an indication of future demand. Mortality data for all deaths from muscular dystrophy registered by death certification in England and Wales between 1993 and 1999 were analysed. In total, 817 deaths from muscular dystrophy were registered between 1993 and 1999. Annual number of deaths was unchanged over this period. Median age at death (interquartile range) for all cause muscular dystrophy increased from 20 (17-42.5) years in 1993, to 26 (17.5-63) years in 1999. Respiratory failure was the primary or contributory cause of death in 82% of cases. Two thirds of these deaths were during acute infection. We can expect 100 patients with muscular dystrophy to develop respiratory failure in England and Wales each year, so non-invasive ventilation services probably need to be able to provide for 0.2 new patients per 100,000 population annually. Respiratory services also need to provide adequate monitoring and early treatment of infection in these patients.

Background: To identify which environmental exposures underpin the emergence of asthma epidemics, we need to study epidemics as they appear, as is now happening in the Jimma region of Ethiopia. We have previously studied risk factors for asthma in adults in Jimma and have now completed a survey of young children., Aim: To establish the prevalence of asthma in urban and rural children in Jimma, and to identify locally important risk factors., Design: Cross-sectional survey., Methods: All children aged 1-5 years living in Jimma town and three surrounding rural regions were identified. Data were collected using an interviewer-led questionnaire, and consenting children had skin prick tests to house dust mite and cockroach., Results: We surveyed 7155 children, of whom 3623 (51%) were female and 4285 (60%) lived in the urban area. The prevalence of wheeze in the last year was 3.4%, and was lower in the rural area (OR 0.47; 95%CI 0.34-0.66). In the urban area, the main risk factors for wheeze were a longer duration of breastfeeding, use of kerosene, and environmental tobacco smoke, while living with animals was protective. In rural children, the main risk factors were a positive skin prick test and living with animals., Discussion: The prevalence of wheeze in children in the Jimma region is low, particularly in rural children. In addition to having an impact on disease prevalence, place of residence also appears to modify the impact of environmental risk factors for wheeze.

Objective: This study examines the effect of including muscle forces in fatigue tests of cemented total hip arthroplasty reconstructions., Design: An experimental device capable of applying the joint reaction force, the abductor force, the vastus lateralis force, and the tensor fasciae latae force to the implanted femur is described., Background: Current in vitro fatigue tests of cemented total hip arthroplasty reconstructions do not apply physiological muscle loads. Experimental and numerical studies report significant differences in stresses obtained in the cement mantle depending on the loads applied. The differing stresses may alter the outcome of an in vitro test., Methods: Ten femoral components were reproducibly implanted into proximal composite femurs. Five of these femoral components were tested using a loadprofile which included muscle loading, five were tested without muscle loading. The migration of each femoral component was monitored continuously during dynamic fatigue tests., Results: Clinically comparable migration amounts were found for both sets of femoral components, with the femoral components tested with muscle loading experiencing lower mean migration, lower mean inducible displacement, and less experimental scatter., Conclusions: The inclusion of muscle forces seems to stabilise the femoral component during the test. In vitro fatigue tests of cemented total hip arthroplasty reconstructions should include muscle loading to provide increased confidence in the results obtained., Relevance: This study examines how the migration of cemented femoral hip prostheses is influenced by muscle forces. Hip prostheses are one of the few medical devices for which pre-clinical testing protocols have emerged, and this study ascertains whether or not the inclusion of muscle forces is necessary for pre-clinical tests. The conclusion that muscle loading should be included, and that it is important for the development of a new generation of standardised tests to provide enhanced patient protection against functionally poor prostheses.

Background: Patients with idiopathic chronic cough and unexplained airflow obstruction in non-smokers have been shown to have an increased prevalence of hypothyroidism and other organ specific autoimmune disorders. Whether patients with hypothyroidism have an increased prevalence of respiratory symptoms is unknown., Methods: The prevalence of respiratory symptoms was assessed in 124 patients with treated hypothyroidism recruited from primary and secondary care, 64 outpatients with inflammatory bowel disease, and 1346 control adults recruited randomly from the electoral register in a case-control study. Respiratory symptoms and smoking history were assessed by a respiratory symptom questionnaire., Results: After adjustment for age, sex and smoking, symptoms of breathlessness and sputum production were more prevalent in both patient populations than in controls (odds ratios for hypothyroidism and inflammatory bowel disease; breathlessness: 3.1 (95% CI 2.1 to 4.6) and 3.4 (95% CI 2.0 to 6.0), respectively; sputum production: 2.7 (95% CI 1.6 to 4.5) and 2.5 (95% CI 1.2 to 5.0), respectively). Cough during the day and night was significantly more prevalent in patients with hypothyroidism (1.8 (95% CI 1.2 to 2.9)) and approached significance in those with inflammatory bowel disease (1.8 (95% CI 1.0 to 3.4)). Wheeze and nocturnal cough were no more prevalent in either disease population than in controls., Conclusion: There is a significantly increased prevalence of respiratory symptoms in patients with hypothyroidism or inflammatory bowel disease compared with controls recruited from the general population. Further work is required to determine whether similar differences are seen in comparison with hospital based controls. These findings support the hypothesis that there is a link between autoimmune hypothyroidism and respiratory disease.

The role of smoking cessation and the use of measures to reduce the disability associated with COPD are reviewed. The political profile of patients with COPD is increasing as patient support groups develop the confidence to campaign for better services.

Asthma is one of the commonest chronic diseases of affluent societies. The striking increase in prevalence of asthma over recent decades and the rarity of this disease in less affluent populations confirms the importance of environmental factors in the cause of asthma--although which environmental factors are responsible is still not clear. Family studies show that genetic factors are also important in determining individual susceptibility to asthma, with results of genetic studies suggesting that there are many genes with moderate effects rather than a few major genes. Asthmatic airways show inflammation and remodelling, with CD4+ helper cells, mast cells, and eosinophils characterising the inflammatory response. Inhaled corticosteroids remain the cornerstone of treatment with the addition of long-acting beta agonists as the next step if symptoms continue. Leukotriene antagonists, the only new drugs to reach the market in the past decade, have modest effects. However, a better understanding of the mechanisms underlying asthma and the genetic and environmental factors that predispose individuals to asthma should lead to better preventative strategies and new therapeutic approaches.

Airway responsiveness and variability in peak expiratory flow (PEF) are widely used as objective diagnostic measures of asthma, but it is not clear how these variables should be calculated or adjusted to obtain the highest diagnostic validity for physician-diagnosed asthma in the community. Data from a community-based sample of 1,513 adults has been used. Airway responsiveness to methacholine and 7-day PEF data were obtained in 1991, asthma and respiratory symptoms were diagnosed by questionnaires in 1991 and 1999. Airway responsiveness was expressed as the provocative dose causing a 20% fall in forced expiratory volume in one second (PD20), two-point and least-squares regression slopes. PEF variability was expressed as daily amplitude, weekly standard deviation and mean of the two lowest readings. Continuous measures were adjusted for measures of baseline airway calibre by linear regression. Measures of airway responsiveness had greater sensitivity for specificity for self-reported diagnosed asthma than expressions of PEF variability, before and after adjustment for airway calibre. Diagnostic validity was substantially better in adults aged <50 yrs; PD20 provided the best sensitivity for specificity (61% for 95% at 8.3 micromol). In those aged > or =50 yrs, no measure was closely related to diagnosed asthma. In younger age groups, provocative dose causing a 20% fall in forced expiratory volume in one second provides a valuable objective measure of asthma for epidemiological studies, but is unable to distinguish between asthma and chronic obstructive pulmonary disease in older people.

Objective: To assess the hypothesis that maternal postpartum behaviors toward the newborn may predict the quality of the maternal-infant relationship during the first year., Design: Prospective, non-randomized, longitudinal cohort study of 174 maternal-infant dyads., Methods: A Postpartum Parenting Behavior Scale (PPBS) was formulated to measure clearly defined observed maternal behaviors toward the infant shortly after birth. The quality of the maternal-infant relationship was assessed at 6 months after birth with the Nursing Child Assessment Satellite Training (NCAST) Feeding Scale and at 12 months after birth with the NCAST Teaching Scale and Ainsworth Strange Situation., Results: The PPBS score correlated significantly with the Feeding Scale score (r =.27, P <.005) and with the Teaching Scale score (r =.23, P <.01). Mothers whose infants were later classified as securely attached in the Ainsworth Strange Situation had higher PPBS scores than mothers of infants classified as insecurely attached (mean +/- SD: 5.18 +/- 1.51 vs 4.63 +/- 1.69, respectively, P <.05). In regression models adjusting for social and demographic factors, the PPBS remained a significant predictor of the Feeding Scale score, the Teaching Scale score, and security of attachment., Conclusions: Maternal behaviors in the immediate postpartum period may aid in predicting quality of the maternal-infant relationship during the subsequent 12 months, suggesting the potential for early identification of suboptimal parenting.

Study Objectives: Eosinophils and neutrophils play major roles, respectively, in the pathogenesis of asthma and COPD, and it is well recognized that levels of these cells in peripheral blood are increased in relation to their pulmonary involvement. However, the relation between peripheral blood cell counts of the other major leukocyte groups and these lung diseases or markers of allergy or airflow obstruction is less clear. We have therefore investigated the association between peripheral blood levels of eosinophils, neutrophils, basophils, monocytes, and lymphocytes and the occurrence of chronic respiratory symptoms, atopy, lung function, and bronchial hyperresponsiveness, and the modifying effect of age, in adults., Design: A cross-sectional general population study., Setting: Data on > 2,000 British adults, who originally participated in a study of diet and lung health, were analyzed using multiple linear and logistic regression to adjust for potential confounders, including age, sex, and smoking history., Results: We found that, like eosinophils, the peripheral basophil count was increased in relation to asthma and associated symptoms, and to airway hyperreactivity and increased total IgE, but differed from eosinophils in that basophils were unrelated to atopy. Monocytes were predominantly associated with symptoms indicative of obstructive airway disease, in similar relation to neutrophils, but both of these leukocyte counts were also increased in asthma patients in older age groups. Lymphocyte counts were unrelated to any objective or subjective marker of disease., Conclusions: If peripheral blood cell counts reflect pulmonary involvement of these leukocyte groups, basophils and monocytes may play a distinct role in the pathogenesis of allergic and nonallergic respiratory disease.

Objective: To evaluate the relationship between early perinatal hospital discharge and several parenting outcomes during infancy, including breastfeeding, mother-infant interaction, and mother-infant attachment., Study Design: A prospective, longitudinal, nonrandomized study of mother-infant dyads discharged 36 hours after birth (late discharge)., Methods: Demographic, perinatal, and psychosocial factors were determined from medical record review and maternal questionnaires. Questionnaires also assessed maternal perceptions of the hospital stay and breastfeeding rates. Mother-infant interaction was assessed at 3 months after birth using the NCAST Feeding Scale and at 9 months after birth using the NCAST Teaching Scale. Security of attachment was measured in the Ainsworth Strange Situation at 12 months after birth., Results: Early and late discharge groups were similar with respect to major demographic, perinatal, and psychosocial characteristics and perceptions of the hospital stay. Even after adjusting for these factors in regression analyses, no significant association was found between early discharge and breastfeeding at 3 months, NCAST scores at 3 and 9 months, and security of attachment at 12 months., Conclusion: Parenting outcomes, such as breastfeeding, mother-infant interaction, and attachment, are not influenced by early perinatal hospital discharge.

This study was designed to examine the organisation and outcomes of a District General Hospital respiratory sleep service, since data are lacking on the management of sleep-disordered breathing at this level. Questionnaires and case-notes review were used to assess the management of 119 consecutive patients referred with suspected sleep-disordered breathing. Patients diagnosed with sleep-disordered breathing were assigned nasal continuous positive airway pressure (nCPAP), ear/nose/throat (ENT) surgery or simple measures (e.g., weight loss). There were six non-attenders. At 12 months follow-up, 33 patients had been assigned to nCPAP, 25 to ENT surgery, and 37 to simple measures. Of the remainder, nine had alternative diagnoses, two were still being assessed and seven were lost to follow-up. Patients prescribed nCPAP (81% compliance) had significant symptomatic improvements with low dissatisfaction rates (20%); patients on simple measures did not improve (33% dissatisfied); only half assigned surgery had it performed, with 42% awaiting surgery and dissatisfied. Interspecialty referral resulted in major delays (mean 16 weeks). Referral letters were generally unhelpful in deciding on the appropriateness of initial referral (respiratory physician vs ENT). nCPAP was generally effective in improving symptoms, with a high level of patient satisfaction, while simple measures did not improve symptoms and were associated with lower satisfaction levels. Waiting times to ENT surgery can be long and patients express significant dissatisfaction. Referral letters are not useful in directing initial referral. Services should be co-ordinated between respiratory and ENT specialties to reduce waiting times and improve patient satisfaction.

Background: It has recently been suggested that measles infection may reduce the risk of atopy., Objective: To study the independent effect of measles infection and measles vaccination on the occurrence of hay fever in a British national birth cohort., Methods: In over 6000 children born in 1970, details of immunizations and childhood diseases were collected by parental interviews at ages 5, 10 and 16 years, and hay fever within the past year at age 16 years., Results: In univariate analysis, hay fever was less common in those contracting measles infection than in those not infected (OR 0.86, 95% CI 0.76-0.96), and more common in those given measles vaccination than in those not vaccinated (OR 1.16, 95% Cl 1.03-1.31). However, these effects were strongly confounded by birth order, which was closely associated with the likelihood of receiving measles vaccination and with the risk of hay fever. A strong interaction between the effects of measles vaccination and infection, and birth order was found, such that in those with many older sibling contacts, hay fever was significantly and independently reduced in relation to both measles infection and measles vaccination relative to those who were neither infected nor vaccinated., Conclusions: Both measles infection and measles vaccination in childhood appear to reduce the risk of hay fever in children with multiple older sibling contacts. Differential exposure or response to the measles virus may explain the effect of birth order on the occurrence of allergic disease.

Birth order, maternal age, gestational age, birth weight, maternal smoking, and social class have all been associated with allergic rhinitis, eczema and asthma in childhood, but the consistency of independent effects of these exposures in relation to all of these allergic conditions has not been investigated. We have compared and contrasted the independent effects of these putative risk factors on parent-reported hayfever, eczema and wheeze by age 16 years and in the past 12 months at age 16 using data from the 1970 British birth cohort. The 1970 British birth cohort comprised all children born in England, Scotland and Wales in one week of April 1970, and follow-up surveys at birth, 5, 10 and 16 years of age involved a cumulative total of 17,427 children. We have used data on over 6000 children with complete data at every stage. Social advantage was a risk factor common to each of wheeze at, and hayfever and eczema at and by age 16. Low birth order was an independent risk factor for eczema and hayfever at age 16, but not for wheeze. However, wheeze at age 16 was significantly increased in relation to maternal smoking, with a significant interaction such that the effect of smoking was greatest in those of high birth order and, in the absence of maternal smoking, low birth order was a risk factor for wheeze at age 16. Social advantage and low birth order appear to be the independently consistent determinants of atopic disease. Maternal smoking is an additional risk factor for wheeze, which applies primarily in low socioeconomic groups.

Background: Although official guidelines and recent legislation have addressed early postpartum hospital discharge and follow-up, little is known about the practices of obstetricians in Canada and the United States on this issue., Methods: Questionnaires were mailed to two separate random samples of 2000 Fellows of the American College of Obstetricians and Gynecologists (ACOG) in the United States and all Canadian Fellows. Practices and perceptions were compared with those recommended in the literature, recent legislation, and guidelines of ACOG and American Academy of Pediatrics (AAP)., Results: In contrast to concerns expressed in the medical literature and official AAP/ACOG guidelines, many physicians considered potential psychosocial and demographic risk factors relatively unimportant in making early discharge decisions, preferring to emphasize aspects of the patient's medical condition, hospital course, and social support. Although the official guidelines encourage follow-up for all patients discharged early, additional visits are routinely advised by only 39 percent of obstetricians after vaginal delivery and by 68 percent after cesarean section. After vaginal delivery 39 percent of obstetricians used telephone follow-up and 37 percent after cesarean delivery. Moreover, although the official guidelines recommend follow-up within 48 hours of discharge, only one-half of the obstetricians surveyed advised follow-up at this time. In contrast to the guidelines, most obstetricians defined early discharge as that occurring within 24 hours after vaginal delivery and 72 hours after cesarean delivery; most defined optimal lengths of stay within the 48-hour (after vaginal delivery) and 96-hour (after cesarean delivery) periods considered short by the guidelines., Conclusions: Current postpartum early discharge and follow-up practices emphasize the physical health of the mother and place little emphasis on social risk. They appear to be influenced by perceptions of the appropriateness of the length of stay and are not in agreement with professional guidelines.

Although evaluation of psychosocial risk factors prior to perinatal hospital discharge has been advocated, the means for accomplishing such an evaluation are not well established. This article reviews several major psychosocial risk factors together with instruments that have been utilized to assess them during the perinatal period. Formal constructs reviewed include anxiety, depression, self-concept, general attitudes, life events, stress, adaptation, social support, marital and family functioning, and the home environment. Ongoing assessment of psychosocial status using formal instruments during routine perinatal care may provide a more complete picture of the psychosocial needs of the individual mother and her family, allowing for more appropriate, timely intervention and utilization of social and health care resources.

With shorter postnatal hospital stays, concern has arisen that many infants may be discharged prior to completion of the transition to extrauterine life, a time of dynamic physiologic change when many neonatal problems may present. This article reviews the physiology of the neonatal transition together with common transitional disorders. Most disorders of transition present at typical postnatal time periods, permitting their timely anticipation and treatment. Moreover, many are associated with factors that may further aid the clinician in defining those infants at highest risk.

Introduction: Neonatal nurse practitioner (NNP) and physician (NCP) use in a community hospital was evaluated to test the hypothesis that NNP availability would result in changing patterns of NCP attendance at newborn resuscitations., Method: Records were reviewed for consecutive years before (pre-NNP) and after (post-NNP) NNP employment for frequency of NNP and NCP attendance at moderate-, high-, and very high-risk deliveries, together with rates of low Apgar scores and resuscitation guideline compliance., Results: Pre-NNP, NCPs attended 39.5% o of moderate-risk and 91.6% of high-risk deliveries; these figures fell to 2.1% and 6.0%, respectively, during post-NNP (chi square: df = l, p < .0001). Post-NNP, NNP attendance at moderate- and high-risk deliveries was 88.6% and 99.2% higher than NCP attendance during pre-NNP (chi square: df = l, p < .01). No difference was observed between periods in rates of Apgar scores less than 7 at 5 minutes or the percentage of resuscitations that complied with current guidelines., Discussion: In community hospitals NNPs may be used instead of NCPs for moderate- and high-risk deliveries. They may also be used more than NCPs in the absence of NNPs.

Objective: To investigate the effect of hospital discharge time on neonatal mortality of term newborns., Design: Infants who were discharged home at 5 days of age of younger and who subsequently died were compared with control infants using a retrospective case-control design. Descriptive information was collected from records of infants who were not discharged home from the hospital of birth (because of death or transfer to a tertiary care hospital) to determine the age at which their illnesses presented., Methods: We reviewed death certificates for all infants with birth weights of 2500 g or greater born at 37 weeks' gestational age or greater who died in the first 28 days of life and who were born in one of four Utah counties (1985 through 1989). Of the 109,256 eligible births, 115 infants were found who had died in the neonatal period. Eighty-four infants had not been discharged home from the hospital of birth, 5 infants had had hospital stays of more than 5 days, 9 records could not be located, 17 presumed healthy infants were discharged from the hospital at 5 days of age or younger. These 17 infants were each matched with 3 control infants. Newborn nursery charts were reviewed to determine hospital discharge times for case and control infants. Descriptive information regarding the time of presentation of illness was collected for the other 89 infants., Results: The mean age of hospital discharge was 43 +/- 21 hours for the 17 case infants and 47 +/- 25 hours for the 51 control infants. The odds ratio for neonatal mortality for discharge at less than 24 hours was 1.65 (95% confidence interval, 0.42 to 3.34) and for discharge at less than 48 hours was 1.16 (95% confidence interval, 0.4 to 3.34). Of the 84 infants who were not discharged home from the hospital of birth, 93% had been symptomatic by 12 hours of age, and 99% were symptomatic by 18 hours., Conclusions: Most full-term infants who die in the neonatal period are symptomatic within the first 18 hours after birth. We could not demonstrate an association between early hospital discharge and neonatal mortality in those infants who died after discharge home.

In six preterm infants we tested the hypothesis that, as is the case in infant rats, orally administered recombinant erythropoietin (EPO) would be absorbed and would stimulate erythropoiesis. Three study subjects were younger than 1 week old and had never been fed and three were more than 1 month old and were receiving enteral feedings totally. Two hours after the administration of large doses of EPO (1000 U/kg body weight) only a small increase in serum EPO concentrations (from 6.3 +/- 0.9 to 13.3 +/- 2.8 mU/ml, mean +/- SEM) was observed. No further increases were observed 4, 6, 12, or 24 hours after the administration. No increases in reticulocyte count or hematocrit were observed after 10 days of EPO administration. We conclude that, unlike the situation in infant rats, enterally administered recombinant EPO is not absorbed in significant amounts by human preterm infants. Therefore oral administration will not be an effective substitute for subcutaneous or intravenous EPO administration in preterm infants.

To determine whether asthma mortality is influenced by geographical or social factors, a retrospective analysis of deaths from asthma in England and Wales between 1979-1987 was performed. Death rates in the 15 Regional Health Authority areas of England and Wales were stratified by sex, age group (0-4, 5-34, 35-64, and > 64 years), and occupational social class. Detailed analysis was restricted to subjects aged 5-64 years because adequate social class data was only available over this age range. Death rates were higher in manual occupational groups (social class IIIb-V) than in non-manual occupations (social class I-IIIa), but on further analysis this effect was confined to males aged 35-64 years. In younger subjects (5-34 years), mortality was higher in the south of the country, and this difference was significant in males (P < 0.05). In older subjects (35-64 years), mortality in both sexes was significantly higher in the north of the country. This study demonstrates that mortality is not evenly distributed between social classes or regions of the country.

We have investigated the relation between lung function and dietary intake of the antioxidant vitamins C and E in the general population in a cross-sectional survey of a random sample of adults from the electoral register of an administrative area of Nottingham. In 2,633 subjects 18 to 70 yr of age, we measured FEV1 and FVC, allergen skin sensitivity to grass pollen, cat fur, and Dermatophagoides pteronyssinus, pack-years smoking exposure by personal recall, and usual dietary intake of vitamins C and E by semiquantitative food frequency questionnaire. After adjustment for the effects of age, sex, height, mean allergen skin wheal diameter, and pack-years smoking history, both FEV1 and FVC were significantly and independently related to mean daily intake of vitamin C, such that a standard deviation (40 mg/d) higher vitamin C intake was associated with a 25.0 (95% CI, 5.2 to 44.8; p = 0.01) ml higher FEV1 and a 23.3 (0.94 to 45.7, p = 0.04) ml higher FVC. There was also an association between vitamin E intake and lung function, such that a standard deviation (2.2 mg) higher intake of vitamin E was associated with a 20.1 (1.3 to 40.4, p = 0.04) ml higher FEV1 and a 23.1 (1.0 to 45, p = 0.04) ml higher FVC. However, vitamin C and vitamin E intakes were significantly correlated (r = 0.29, p < 0.001), and after allowing for the effects of vitamin C there was no additional independent effect of vitamin E on either FEV1 or FVC.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Pulmonary lymphangioleiomyomatosis is a rare progressive disease of unknown aetiology affecting premenopausal women. Since the oral contraceptive pill has been implicated in its pathogenesis, a case control study was carried out to determine whether women with the disease were more likely to have taken the oral contraceptive pill, and whether the disease was associated with other conditions related to sex hormones including pregnancy, parity, and fibroids., Methods: All chest physicians in the UK were asked for details of all live patients with pulmonary lymphangioleiomyomatosis; the patient's family doctor was then asked for four age and sex matched control subjects from their patient register. Details of lifetime use of the oral contraceptive pill, pregnancy, parity, history of fibroids, and smoking were obtained from cases and controls. Relative odds of exposure to potential risk factors were estimated by conditional logistic regression., Results: Medical details were obtained from all 23 cases of lymphangioleiomyomatosis identified; questionnaires were completed by 21 cases (one by proxy) and by 46 matched controls of mean (SD) age 43 (10) and 44 (11) years, respectively. The patients had a mean age of 34 (9) years at onset of symptoms and a median (range) time of 2 (0-29) years from onset of symptoms to diagnosis. Compared with control subjects, cases did not differ in the use of the oral contraceptive pill (odds ratio (OR) 0.39, 95% CI 0.09 to 1.68), diagnosis of fibroids (OR 3.12; 95% CI 0.52 to 18.7), age of menarche, menstrual history, or lifetime smoking. They were, however, less likely to have been pregnant (OR 0.14, 95% CI 0.03 to 0.71) or to have had children (OR 0.13, 95% CI 0.03 to 0.67). More pregnancies had ended in spontaneous abortion (28% v 8%) but the proportion of women undergoing spontaneous abortion was similar in cases and controls (OR 2.13, 95% CI 0.47 to 9.3)., Conclusions: This study does not support the hypothesis that use of the oral contraceptive pill is causally associated with the development of pulmonary lymphangioleiomyomatosis. Sex hormones may be involved, however, since patients were less likely to have been pregnant or to have had children, and tended to have had more spontaneous abortions and an increased incidence of fibroids.

Objective: To provide the pediatric practitioner with a summary of available data regarding the appropriate time of hospital discharge of the term newborn., Methodology: Published series on early discharge were critically reviewed., Results: Heterogeneity and limitations of methodology and study design substantially limit conclusions that may be drawn from published studies., Conclusion: Early discharge recommendations of the American Academy of Pediatrics remain appropriate, and decisions regarding the timing of discharge of the well term newborn should be individualized and made by the practitioner based upon the medical, social, and economic aspects of each case.

Heart-lung transplantation has become an established treatment for end stage respiratory failure secondary to cystic fibrosis. The success of this form of treatment, and the increasing survival of such patients, suggests there will be an increased need for transplantation over the next decade. We have used cystic fibrosis population predictions and all cause mortality data to estimate the number of cardio-pulmonary deaths, due to cystic fibrosis, over the next decade and to estimate the number of such patients who are likely to benefit from heart-lung transplantation. We estimate that there will be between 85 and 127 potential transplant recipients with cystic fibrosis each year over the next decade. During 1990, 1991 and 1992 there were less than 40 transplants each year in such patients. These data emphasize the need to expand transplantation services and to maintain the availability of donor organs.

Background: Bronchial reactivity measurements are widely used in epidemiological studies to provide an objective marker of asthma. There are, however, several potential advantages of measuring peak expiratory flow (PEF) variability instead, particularly in large studies. PEF variability and bronchial reactivity were compared in a population sample to assess the relationships of the two measurements to factors known to be associated with airways disease, and to compare their response rates., Methods: Subjects aged 18-65 were randomly selected from the electoral register of an administrative area in eastern England and randomised to attend either for a bronchial challenge test measuring the provocative dose of methacholine producing a 20% fall in FEV1 (PD20), or to measure PEF at two hourly intervals during waking hours for one week. Skin tests with common allergens were performed and a smoking history obtained. PEF variability was expressed as the amplitude % mean (highest - lowest x 100/mean)., Results: A total of 273 subjects (69%) collected a PEF meter but a completed record sheet was returned by only 247 (62%); this was still significantly more than the 202 subjects (54%) who attended for and successfully completed a challenge test. Amplitude % mean was higher in women than in men (9.7% v 8.5%). In multiple regression analysis amplitude % mean increased significantly with age, mean skin weal diameter, and with current smoking. The odds of having a PD20 below 24.5 mumol increased with mean skin weal diameter and were greater in current smokers. Neither age nor sex had a significant effect on bronchial reactivity but there were significant interactions between age and the effects of both smoking and atopy., Conclusions: The higher response rate associated with the use of PEF variability measurement, and the association with factors implicated in the pathogenesis of airways disease, suggest that PEF variability would be a useful measurement to employ in epidemiological studies.

Nedocromil sodium is a non-steroidal prophylactic agent developed for the management of asthma. We have assessed the steroid sparing potential of inhaled nedocromil sodium 4 mg four times daily in a randomized, double blind, placebo controlled study in 69 asthmatic subjects controlled on inhaled beclomethasone dipropionate in the dose range 1000-2000 micrograms daily. Following a 4 week run-in period subjects added nedocromil sodium or placebo by metered dose inhaler to their usual medication for a further 4 weeks. The dose of inhaled steroid was then reduced at fortnightly intervals according to a predetermined schedule, with monitoring of asthma severity, symptom scores, bronchodilator use and peak flow recordings. Sixty subjects entered the steroid reduction phase and achieved median (range) % decreases in steroid dose of 80 (17-100)% with nedocromil sodium compared to 65 (0-100)% with placebo (P = 0.34) with 14 patients in the nedocromil sodium group and 10 in the placebo group being withdrawn completely from inhaled steroids. Subjective global assessment scores were significantly better with nedocromil sodium (mean 2.14) than with placebo (2.93; P < 0.02) though there was no difference between individual daily symptom scores. In this study therefore in asthmatic patients controlled on high doses of inhaled steroids, nedocromil sodium was well tolerated but the small differences in steroid sparing effect between nedocromil and placebo were not statistically significant.

Bronchial responsiveness to histamine or methacholine provides a useful objective measure for epidemiological studies of airways disease, but most people in a community population do not have a 20% fall in forced expiratory volume in one second (FEV1) with the highest dose administered. Histamine challenge data were analysed to compare the repeatability. Normality and separation of symptom groups of the early dose-response slope with provocative dose producing a 20% fall in FEV1 (PD20). Tests were continued until a 20% fall in FEV1 occurred, or 4 mumol had been given. Data were available for 510 randomly selected subjects, and for an additional 283 with wheeze. A repeat test was obtained in 104 individuals. PD20 was estimated by curve fitting, with extrapolation to 8 mumol. Least-squares slope of percentage decline in FEV1 on histamine dose was calculated, using all the measured points and two-point slope as the fall from the post-saline measurement to the maximum cumulative dose divided by the maximum dose. Log transformation of PD20 and shifted reciprocal transformations of slope produced constant variance. Over all subjects the three measures had similar repeatability; in subjects with PD20 > 8 mumol the intraclass correlation for two-point slope was only 0.26, but was 0.66 for least-squares slope. Neither measure of slope was normally distributed, but the distribution of log(PD20) was consistent with a censored normal distribution. In conclusion, least-squares slope is preferable to two-point slope for epidemiological studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Standard percentile curves are presented for weight, length, head circumference and chest circumference at birth for a population of 27,963 singleton infants born between the gestational ages of 26 and 42 weeks at a large, private hospital in Phoenix, Arizona. At term, all four growth parameters were significantly greater in male than in female infants. These parameters were significantly reduced in infants born to mothers who smoked and increased in infants born to mothers with diabetes. Percentiles in all parameters were higher than in those of previous studies, suggesting that continued use of growth curves based on older data may result in misclassification of infants with respect to appropriateness of growth-for-gestational age.